1 We have compared the signalling mechanisms involved in the pertussis toxin-sensitive and -insensitive contraction of rat isolated mesenteric microvessels elicited by sphingosylphosphorylcholine (SPC) and noradrenaline (NA), respectively. 2 The phospholipase D inhibitor butan-1-ol (0.3%), the store-operated Ca 2+ channel inhibitor SK&F 96,365 (10 mM), the tyrosine kinase inhibitor genistein (10 mM), and the src inhibitor PP2 (10 mM) as well as the negative controls (0.3% butan-2-ol and 10 mM diadzein and PP3) had only little e ect against either agonist. 3 Inhibitors of phosphatidylinositol-3-kinase (wortmannin and LY 294,002, 10 mM each) or of mitogen-activated protein kinase kinase (PD 98,059 and U 126, 10 mM each) did not consistently attenuate NA-and SPC-induced contraction as compared to their vehicles or negative controls (LY 303,511 or U 124). 4 The phospholipase C inhibitor U 73,122 (10 mM) markedly inhibited the SPC-and NA-induced contraction (70% and 88% inhibition of the response to the highest NA and SPC concentration, respectively), whereas its negative control U 73,343 (10 mM) caused only less than 30% inhibition. 5 The rho-kinase inhibitors Y 27,632 (10 mM) and fasudil (30 mM) caused a rightward-shift of the NA concentration-response curve by 0.7 ± 0.8 log units and reduced the response to 10 mM SPC by 88% and 83%, respectively. 6 These data suggest that SPC and NA, while acting on di erent receptors coupling to di erent G-protein classes, elicit contraction of rat mesenteric microvessels by similar signalling pathways including phospholipase C and rho-kinase.

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